Porphyrins and related tetrapyrrolic macrocycles have application in various medical procedures for the diagnosis and treatment of disease.
Magnetic Resonance Imaging (MRI) is a process in which a particular object to be viewed is exposed to a radio frequency while in the presence of a varying magnetic field. In general, MRI utilizes contrast agents to produce cross-sectional images for medical diagnosis. The use of contrast agents allows one to differentiate the target tissue of interest from the surrounding tissue in the image. The use of contrast agents with MRI, however, suffers from several limitations. For example, one major limitation of the use of certain contrast agents is the disassociation of the metal from the metal complex of the contrast agent, which can leave toxic levels of metals within the body of an patient.
Positron Emission Tomography (PET) is a type of tomography produced by the detection of gamma rays emitted from tissues after the administrations of a natural biochemical substance into which positron-emitting isotopes have been incorporated. A major limitation of the use of certain contrast agents with PET is the disassociation of the radioactive isotopes from the agent, which can leave toxic levels of radioactive elements within the body of an patient.
Porphyrins and related tetrapyrrolic macrocycles also have application in the field of Photodynamic Therapy (PDT). PDT is a technique that utilizes photosensitive compounds that have a selective affinity for diseased tissue and which accumulate in diseased tissue to a greater extent than in normal tissue. PDT involves the localization of a photosensitizing agent in or near a diseased target tissue within the body. The photosensitive compound, upon illumination and in the presence of oxygen, produces cytotoxic species of oxygen such as singlet oxygen or oxygen radicals, which destroy the diseased target tissue. The PDT technique provides a greater degree of selectivity or specificity not currently achievable with current methods of chemotherapy.
Heterocyclic carbenes have been found to be useful as complexing ligands for a wide variety of metals to produce corresponding ligand-metal complexes having good thermal and chemical stability.
The synthesis of transition metal complexes of imidazol-2-ylidenes, also known as N-heterocyclic carbenes, was first pioneered by Ofele and Wanzlick in 1968 and is a very active area of research today. The synthesis of free isolable N-heterocyclic carbenes and their complexation with transition metals was first reported by Arduengo in 1991. It is not always convenient, however, to synthesize complexes from free carbenes and transition metals. A recent advance is the use of silver bis(carbene) complexes as carbene transfer reagents.
A process for the preparation of heterocyclic carbenes is described in U.S. Pat. No. 6,025,496 to Hermann et al.
Therefore, the needs exists in the art to develop improved ligands and ligand-metal complexes for diagnostic and therapeutic applications.